Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000234101 | SCV000289048 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with histidine at codon 1040 of the RAD50 protein (p.Gln1040His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs778106950, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV000234101 | SCV001179979 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-18 | criteria provided, single submitter | clinical testing | The p.Q1040H variant (also known as c.3120A>C), located in coding exon 20 of the RAD50 gene, results from an A to C substitution at nucleotide position 3120. The glutamine at codon 1040 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |